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Anticoagulant agents have been approved by international regulatory agencies to prevent and treat venous thromboembolism (VTE). However, chronic kidney disease (CKD) is: (1) highly frequent in VTE patients; (2) strongly linked to VTE; and (3) a risk factor for cardiovascular morbidity/mortality and fatal pulmonary embolism. Therefore, an increasing number of patients are presented with CKD and VTE and more and more physicians must face the questions of the management of these patients and that of the handling of anticoagulant agents in CKD patients because of the pharmacokinetic modifications of these drugs in this population. These modifications may lead to overdosage and dose-related side effects, such as bleeding. It is therefore necessary to screen VTE patients for CKD and to modify the doses of anticoagulants, if necessary., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) are now in competition. The companies are trying to replace VKA by DOACs, totally or at least greatly VKA should VKA disappear in favor of DOACs? There are still many questions about DOACs. The purpose of this article is to make a well-considered decision in this area. The aim is not to denigrate one or the other but to share things between these two families of anticoagulants. Physicians using these drugs must have a full knowledge about compared efficacy and safety. We feel necessary to increase distance between effective results of the clinical trials and industrial communication around DOACs., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Cancer and venous thrombo-embolic disease (VTE) are closely related. Indeed, cancer can reveal VTE and VTE can be the first sign of cancer. Low molecular weight heparin (LWMH) is now the first line treatment in cancer patients. Compliance with marketing authorizations and guidelines are crucial for patient-centered decision-making. This work deals with the prescription of LWMH in patients who develop VTE during cancer in order to better recognize what should or should not be done. The patient's wishes must be taken into consideration when making the final therapeutic decision. The other treatments are discussed: vitamin K antagonists and direct oral anticoagulants (DOACs) may be useful., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

On the 4th of December 2015, the French authorities officially recognized the birth of a specialty in vascular medicine entitled CO-DES cardiology-vascular/vascular Medicine. France is the 7th country to obtain this specialty after Switzerland, Germany, Austria, Czech Republic, Slovakia and Slovenia, six countries in the EEC. It has taken years to achieve a long but exciting experience: we went from hopes to disappointments, sometimes with the blues, but lobbying helping… with sustained confidence. This article tells the story of 30 years of struggle to achieve this vascular medicine specialty. Gaston Bachelard wrote: "Nothing is obvious, nothing is given, all is built." For the construction of vascular medicine, we had to overcome many obstacles, nothing was given to us, everything was conquered. Beware "The specialist is one who knows more and more things about an increasingly restricted field, up to 'knowing everything about nothing"' recalled Ralph Barton Ferry, philosopher; so there is room for modesty and humility but also convictions. The physical examination will remain the basis of our exercise. But let us recall the contributions of all those vascular physicians who practiced in the past, together with those currently active, who built day after day, year after year, a vascular medicine of quality. It is because of the trust of our colleagues and our patients that we can occupy the place that is ours today., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Carotidynia is rare and associates neck pain with tenderness to palpation usually over the carotid bifurcation, the diagnosis of which is based on magnetic resonance imaging (MRI). Ultrasounds (US) are also frequently used but their accuracy in predicting the course of the disease is unknown. We are reporting the case of a 52-year-old man who presented a typical carotidynia. Clinical symptoms, ultrasound and MRI imaging evolution were closely correlated. Our case suggest that after a first MRI to set a positive diagnosis of carotidynia and exclude differential diagnoses, US which is more widely available and less expensive could constitute the imaging of reference for the follow-up., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Although aneurysm of the abdominal infra-renal aorta (AAA) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free AAA ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of AAA. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of AAA in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected AAA was 33 mm (range 20 to 74 mm). The prevalence of AAA was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for AAA (Vesalius operation 2014/2015) in order to increase public and physician awareness about AAA detection, therapeutic management, and monitoring. AAA is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Lasers are increasingly used to treat vascular abnormalities. Indeed, this technique is non-invasive and allows a specific treatment. The aim of this review is to present some biophysical principles of the lasers, to describe the different sorts of lasers available for treatment in vascular medicine indications. Three principal lasers exist in vascular medicine: the pulsed-dye laser, for the treatment of superficial pink lesions, the NdYAG-KTP laser for purple and bigger lesions, and the NdYAG long pulse laser for even deeper and bigger vascular lesions. In vascular malformations, port wine stains can also be treated by pulsed-dye laser, KTP or NdYAG when they are old and thick. Telangiectasias are good indications for the three sorts of lasers, depending on their depth, color and size. Microcystic lymphatic malformations can be improved by laser treatment. Arterio-venous malformations constitute a contraindication of laser treatment. In vascular tumors, involuted infantile hemangiomas constitute an excellent indication of pulsed-dye laser treatment. Controlled studies are necessary to evaluate and to compare the efficacy of each laser, in order to determine their optimal indications and optimal parameters for each machine., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

THE QUALITY STANDARDS OF THE FRENCH SOCIETY OF VASCULAR MEDICINE FOR THE ULTRASONOGRAPHIC ASSESSMENT OF VASCULAR MALFORMATIONS ARE BASED ON THE TWO FOLLOWING REQUIREMENTS: Technical know-how: mastering the use of ultrasound devices and the method of examination. Medical know-how: ability to adapt the methods and scope of the examination to its clinical indication and purpose, and to rationally analyze and interpret its results. AIMS OF THE QUALITY STANDARDS: To describe an optimal method of examination in relation to the clinical question and hypothesis. To achieve consistent practice, methods, glossary, and reporting. To provide good practice reference points, and promote a high-quality process. ITEMS OF THE QUALITY STANDARDS: The three levels of examination; their clinical indications and goals. The reference standard examination (level 2), its variants according to clinical needs. The minimal content of the examination report; the letter to the referring physician (synthesis, conclusion and proposal for further investigation and/or therapeutic management). Commented glossary (anatomy, hemodynamics, semiology). Technical bases. Settings and use of ultrasound devices. Here, we discuss the methods of using ultrasonography for the assessment of peripheral vascular malformations and tumors., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Peripheral arterial disease (PAD) is an important predictor of cardiovascular disease with major medico-economic consequences. However, systematic screening of asymptomatic patients free from history of cardiovascular disease is debated., Objective: Determining the prevalence, risk factors for PAD in a population of outpatients at intermediate or high-risk of cardiovascular disease, free from history of cardiovascular disease to assess the potential impact of PAD screening in such groups of patients., Methods: Multicenter 1-day screening program of PAD conducted from 2008 to 2010 in a population defined by diabetes plus age greater than 50 years, positive active smoking status, or age greater than 70 years. PAD was defined as an ankle-brachial index (ABI) less than 0.9 measured as follows: lowest systolic ankle pressure divided by highest systolic arm pressure., Results: Ten thousand six hundred and fourteen patients fulfilled study inclusion criteria: 16.7% (n = 1774) exhibited an ABI less than 0.9 and 3.8% (n = 407) an ABI less than 0.7. ABI greater than 1.3 was found in 7.7% of patients (n = 818). Age greater than 70 years, male gender, active smoking status, hypertension and diabetes (treated) were independent risk factors for PAD., Conclusion: Primary prevention outpatient screening of a population with intermediate or high cardiovascular risk can identify numerous patients with PAD. The medical impact in terms of cardiovascular mortality and morbidity of such a screening needs to be assessed., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In vascular medicine, venous insufficiency, ocre dermatitis, stasis dermatitis, or lipodermatosclerosis (level C4 in CEAP) may lead to skin lesions involving the lower limbs. Generally, symptoms resolve with etiologic treatment using medical compression, varicosis treatment, or dermocorticoids. However, some skin lesions progress, suggesting another diagnosis, including a specific dermatosis. The diagnosis is based on clinical, biological, radiological and histological criteria. Referral to a dermatologist may be necessary to determine the appropriate etiological treatment., (© 2011 Elsevier Masson SAS. All rights reserved.)

Long-term post-surgery follow-up is an essential part of the surgical and medical care for vascular surgery patients with peripheral arterial disease. Close collaboration with the patient's primary care physician is essential. In addition to close surveillance of the outcome after vascular surgery, follow-up includes an assessment and appropriate treatment of cardiovascular risk factors. Duplex ultrasound is a safe and noninvasive surveillance method, which should be performed by an experimented physician. We summarize the specific features of duplex ultrasound examinations after arterial surgery of the carotid arteries, the abdominal aorta and the lower limbs, and propose a surveillance schedule., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Mondor's disease is a rare cause of superficial thrombophlebitis, which is very exceptionally observed in the penis. Usually a benign condition, careful etiological search is needed to avoid missing exceptional causes. Mondor's disease is generally treated with non-steroidal anti-inflammatory drugs or low-molecular-weight heparin and resolves without sequelae. Mondor's disease and superficial venous thrombosis of the penis may or may not be a unique clinical entity. A favorable outcome with no precise etiology would favor penile Mondor's disease., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Ankylosing spondylarthritis and Takayasu aorto-arteritis are two inflammatory diseases with a not yet elucidated pathogenic mechanism. Their association is quite exceptional with only a few cases (14) being published in the literature. We report a new case in a 26-year-old woman whose Takayasu disease led to stenosis of the subclavian artery and the thoracic aorta 9 years after diagnosis of ankylosing spondylarthritis with sacro-iliac involvement. This association is probably not fortuitous., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Calf vein thrombosis corresponds to infrapopliteal deep vein thrombosis which accounts for roughly 50% of all cases of deep vein thrombosis and shares the same risk factors as proximal deep vein thrombosis. The complication rate and proper management remain debated. Recent studies suggest that the risk of proximal extension of calf vein thrombosis is 1 to 5% and that the risk of postthrombotic syndrome is 3%. In France, calf vein thrombosis is usually treated with compression stockings associated with a six week to three month regimen of anticoagulation therapy in patients presenting a transient triggering factor or longer otherwise. However, the benefit of such treatment, in terms of the hemorragic risk incurred, remains uncertain. The randomized double blind trial CACTUS (compression stocking + placebo versus compression stocking + heparin, for six weeks) that will start in September 2007, should provide answers the following question: should calf vein thrombosis be treated with anticoagulants?

The preoperative evaluation before coronary bypass led to the discovery of complete atheromatous obstruction of the internal carotid artery sinus in a 79-year-old man free of any neurological symptom. Downstream from the carotid sinus, the patency of the internal carotid artery was ensured by a collateral branch fed by the ipsilateral external carotid artery. This exceptional anatomic variation can be explained by a persistent embryonic artery. The recognition of this atypical feature is clinically relevant because surgery may be possible in some cases, while it is not technically feasible in patients with total obstruction.

Thromboembolic events are an increasingly commonly recognized secondary complications in children treated for serious, life-threatening primary diseases. Nevertheless the incidence of venous thromboembolic disease remains 100 times less frequent in hospitalized children than hospitalized adults, as recent data suggest an incidence of 5,3/10.000 pediatric patients compared to an incidence of 2,5-5/100 in adult patients. Diseases usually associated with thromboembolic events in children are neoplasia, autoimmune or cardiac malformative disease. Contrarily to what is observed in the adult, the majority of deep vein thrombosis events occur at the upper limbs veins, usually at the place where devices for venous access like port-a-cath or central venous lines are inserted. Because of the relatively low incidence of venous thromboembolic events in children, the diagnostic approach used are largely extrapolated from guidelines obtained from adult studies. However, the diagnostic performances of some diagnostic tools like Doppler-Ultrasound are probably diminished in children. Moreover, the concept of developmental hemostasis, which stresses the point that the hemostatic system in children is quite different from the adult one, is widely accepted and clearly suggests that the diagnostic and therapeutic approach in pediatric patients may not be simply extrapolated from data obtained in adult studies. From a more practical point of view, the fact that the hemostatic system in children is a dynamic and evolving system, renders the therapeutic approach quite complex. In particular, doses of anticoagulants vary markedly across the pediatric age. The absence of adapted formulations of commonly used anticoagulants, for example the absence of liquid formulations of anti-vitamin K drugs, further complicates the administration and the correct monitoring of anticoagulation in children, and may diminish observance in adolescent patients. Even though the concept that "children are not little adults" is nowadays widely accepted, there is an urgent need for prospective studies to better assess the modalities of diagnosis and treatment of venous thromboembolic disease in this particular population.

Unlabelled: Venous thromboembolism (VTE) is a frequent disease and remains a major cause of mortality and morbidity among our patients. During the 20 past years, clinical description, diagnostic tools, and treatment have changed dramatically. Most published data describing risk factors for VTE no longer apply to the patients seen in daily practice. We present here the rationale, aims, and methodology of the OPTIMEV Study (OPTimisation de l'Interrogatoire pour la Maladie thromboEmbolique Veineuse)., Rationale: Risk factors for VTE are numerous, complex and interactions between them and their clinical importance is difficult to measure (table I). For example, odds ratios for VTE recurrence vary greatly across longitudinal studies. We searched the National Library of Medecine (PubMed) and the Amedeo website using the following keywords: "venous thromboembolism", "pulmonary embolism", "deep vein thrombosis", "risk factors". We selected 84 relevant articles published between 1972 and 2005. Based on this literature analysis, we identified the following major risk factors: VTE recurrence, surgery, cancer, immobilization, age, biological factors. For these factors, data are lacking and some questions are proposed., Objectives: The broad objective of the study is to better evaluate clinical risk factors that fit today's practice against VTE. Specific aims are: 1) to determine whether risk factors are different between proximal and distal deep vein thrombosis (DVT); 2) to develop and prospectively validate a new prediction rule for outpatients. The primary hypothesis is that careful assessment of VTE recurrence, adequate surgical thromboprophylaxis, cancer staging, and varicose vein stratification according to the CEAP classification, is mandatory for accurate evaluation of thromboembolic disease risk., Methods: We conducted a multicenter, prospective, cohort study of 10000 patients. Enrollees are inpatients and outpatients presenting with a clinical suspicion of VTE in Emergency Departments and outpatient clinics in France. 4173 patients have been enrolled at this time (Figure 2). All eligible patients are enrolled during a selected period of time through different seasons. Data are collected by physicians in charge of the patients using an electronic case recording form. Collected data include baseline characteristics, risk factors, results of diagnostic investigations. Outcome measures obtained through telephone interview at 3 and 12 months include cancer diagnosis, VTE recurrence, haemorrhagic events, treatments, death. Univariate and multivariate analysis will be performed using multilevel logistic regression. The study organization is performed by the Centre d'Investigation Clinique de Grenoble and is sponsored by the French Society of Vascular Medicine. First results, to be published in 2006, will allow development of new prediction rules for VTE diagnosis.

The incidence of iatrogenic femoral false aneurysms has risen dramatically in recent years and is estimated at 0,5% for diagnostic procedures and may rise to 9% or more for therapeutic procedures. This increased incidence is related to the increased number of arterial punctures performed for diagnostic or therapeutic purposes and their major complexity and duration. Risk factors for the development of iatrogenic false aneurysms include operator inexperience, age greater than 60, female gender, catheter size greater than 8F and concurrent anticoagulation. Prevention of false aneurysms is based upon an atraumatic arterial puncture, good compression therapy after sheath removal and use of percutaneous arterial closure devices. Contrarily to the arterial lesions following severe injuries, the natural course of false aneurysms is quite benign with spontaneous occlusion in the majority of cases. Therefore, a mandatory surgical approach is no longer advocated and alternative therapeutic options have been proposed. These include sonographic surveillance, compression ultrasonography, percutaneous thrombin or coil embolization. Surgery is still clearly indicated in presence of local nervous or venous compression, associated homolateral lower limb ischemia, great size of the aneurysm, and unsuccessful non-invasive treatment. Sonographic surveillance has shown to be safe in hospitalized or ambulatory patients. However, fear of aneurysm rupture and cost of repeated ultrasonographic exams preclude widespread utilisation. Compression ultrasonography is safe and effectiveness varies between 70 and 100%, according to studies. Compression ultrasonography may be painful, has often to be associated with mild analgesia, is time consuming and less effective in presence of concurrent anticoagulation. Thrombin injection seems particularly effective, is painless and has a limited rate of complications in expert hands. Severe anaphylactic reactions and severe coagulopathy in reexposed patients have been described and represent clear contra-indications to thrombin injection. Coil embolization of the false aneurysm is as effective as thrombin injection and is reported in a limited number of patients. There is no formal consensus about treatment of the vast majority of non-surgical false aneurysms. In an absence of stringent indication to surgical approach, compression ultrasonography may be used first as it is widely available, and does not require highly specialized skills. Compression therapy should be done after a transient interruption of anticoagulant treatment, if allowed by clinical context. If compression therapy fails, percutaneous injection of thrombin or coil embolization are effective and associated with a low complication rate. However, these techniques are less widely available and necessitate an experienced operator. As recurrences have been described with each of these techniques, every non-surgically-treated false aneurysm should be monitored for 24 hour with ultrasonography control to ensure effective thrombosis.

Revascularisation of the lower limbs with vein graft is frequent. Femoro-popliteal infrainguinal bypass have good permeability rates at five years. The weak point of autogenous vein bypass grafting is vein graft stenosis, which develops particularly in the first post-operative year. Stenoses are mostly in relation with myo-intimal hyperplasia and are often located at anastomoses. Serial arteriography and echographic studies have shown that the development of intrinsic graft stenosis is found in 20 to 30% of vein conduits in the lower extremity. On the basis of an abundance of clinical data, Duplex ultrasound surveillance of infrainguinal vein graft to detect and repair such lesions before graft occlusion is widely accepted and has shown in many retrospective studies to have a positive influence on lifetime of venous grafts. Critical stenosis (peak systolic velocity (PSV) > 300 cm/s and velocity ration (VR) > 4) should undergo surgical revision as it heralds occlusion of the vein graft in short delays. Intermediate stenosis (peak systolic velocity (PSV) 200-300 cm/s and velocity ratio (VR) 2-4 should be accurately followed as 50 to 70% progress to critical stenosis. Use of echo-doppler monitoring is supported by one randomised study which showed superiority of ultrasound surveillance over clinical surveillance, and by a well described relation between graft thrombosis and an increased amputation rate. In contrast, Duplex ultrasound surveillance for prosthetic grafts is not widely accepted primarily because of the occurrence of rare intrinsic lesions in prosthetic grafts, compared to in vein grafts. Vascular doctors are increasingly concerned with the costs of surveillance program and of surgical interventions. Recent economic appraisal have shown that cost associated with graft maintenance is significant, particularly in the first-year and demands consideration. However revision of a duplex-identified stenosis seems to be less costly than revision after graft thrombosis. Costs of limb amputation and the following expense of postamputation rehabilitation are very high and justify limb-salvage-related expense. The results of an ongoing randomised controlled trial (the Vein Graft Trial) comparing duplex ultrasound surveillance against clinical surveillance only will certainly bring more data on the benefits of echographic surveillance.

Objective: To validate ultrasonographic quantification and characterization criteria for aneurysms of the abdominal aorta (AAA) by comparing computed tomography data and surgical findings in order to standardize diagnosis and follow-up of AAA., Patients and Methods: A multicentric prospective study included 80 patients with AAA (January to August 1996). Standardized data on quantitative (diameter, surface area) and qualitative (topography, form, wall, thrombus) data were obtained at each ultrasound examination and at surgery. Ultrasound (US) and computed tomography (CT) explorations were performed and interpreted without prior knowledge by independent operators. US findings versus CT reference were compared in 77 cases, US findings versus surgical reference in 31, and CT findings versus surgery reference in 28., Results: Compared with CT-scan, B mode ultrasound (n = 77) underestimated the anteroposterior diameter of the aneurysm (mean difference -2.16 mm; p < 0.001), the anteroposterior diameters of the flow channel lumen (-5.54 mm; p < 0.001) and upper neck of the aneurysm (-2.74 mm; p < 0.001). Surface area measurements were not significantly different both the aneurysmal sac (p = 0.3) and the flow channel lumen (p = 1). Compared with surgical findings, US (n = 30) underestimated the transverse diameter (mean difference (-4.29 mm; p = 0.0037). Compared with surgery, US findings (n = 28) were not significantly different for the anteroposterior ans transverse diameters. Analyzing the form and wall of the AAA, US/CT-scan performance was good for symmetrical fusiform aneurysms (sensitivity 77%, specificity 67%). US and CT-scan were reliable for detecting wall bugles (same sensitivity, 29%). The angle formed by the thrombus with the wall (expressed in degrees) was not significantly different (p = 0.9). When the lower pole of the aneurysm was situated above the aortic bifurcation, US (sensitivity 75%) was more reliable than the CT-scan (sensitivity 50%) compared with surgical findings., Conclusion: Ultrasonography should not be limited to the simple positive diagnosis of AAA. A precise analysis of the diameters and surface areas of the aneurysm should be performed.

B Mode and TM mode Imaging are useful tools to illustrate directly the venous valve motion. Using B Mode, venous valve are echogenic with a particular kinetic as regards its topography. So it's possible to determine in TM Mode a "pseudo-cardiac" valvular motion (jugular vein) and a "pseudo-diaphragmatic" motion for the lower limbs veins. Valvular motion assures unidirectional venous flow.

Manual lymphatic drainage is used in physiotherapy of limb lymphedema in combination with other physical techniques. In order to assess the effectiveness of the method, 47 patients with upper limb lymphedema after radiosurgical therapy for breast cancer underwent lymphoscintigraphy. The examination was performed after subcutaneous injection of technetium-labeled colloid via the fourth and first interdigital space on the hand of the limb with lymphedema. The level of the technetium label was compared on scintigraphies performed before and after manual lymph drainage. Results were analyzed as a function of the clinical characteristics of the edema. Manual lymphatic drainage produced an effective progression of the label in 25 cases (53.2%), independent of radiotherapy. Contralateral lymph nodes were reached in 5 cases and the homolateral internal mammary nodes in 2. These nodes were visualized only after manual lymphatic drainage. The visualization of the drainage routes in unexpected areas demonstrated the effectiveness of the technique in stimulating accessory routes useful for resorption of lymphedema. The use of two injection sites on the hand is also discussed. This study demonstrated the effect on a single session of manual lymphatic drainage and should be completed with an assessment of a complete series of manual lymphatic drainages.

Portal blood volume was non invasively evaluated with pulsed Doppler ultrasound coupled with automatic, water path echotomography (U. I. Octoson). This measurement was successful in 18 from 24 normal volunteers, the portal flow values being 14.25+ or -4.5 ml/min/kg. The portal blood flow measurement was possible in 16 from 17 patients with hemopathy. Portal flow volume was greatly increased in 11 cases (more than 23 ml/min/kg), in connection with splenomegalia. It was moderately high in 3 cases, from whom 1 without splenomegalia and 1 splenectomised. Portal flow was normal in 1 case and was reduced in 1 case (with high splenic blood flow, in a patient with portal hypertension due to portal vein compression by adenopathy). Portal blood flow increase seems to be connected with splenomegalia. Manometric portal hypertension seems to be more clearly connected with hepatic invasion by hemopathy.